Project description DEENESFRITPL Circadian rhythms and their links to brown adipose tissue thermogenesis Brown adipose tissue (BAT) is a major source of heat production with significant energy-dissipating capacity, presenting a promising target to fight obesity and diabetes. A recent study discovered a novel link between circadian rhythm and thermogenic stress in the control of the calorie-burning function of BAT. Importantly, the circadian and thermogenic signalling to BAT incorporates blood-borne hormonal and nutrient neuronal input. The goal of the ERC-funded aCROBAT project is to investigate this signalling crosstalk that allows mammals to effectively employ daily rhythms in BAT metabolism while adapting to changes in energy demand. A better understanding of these mechanistic insights may uncover the pharmacological targets to harness the energy-expending potential of BAT for the prevention and treatment of obesity and diabetes. Show the project objective Hide the project objective Objective Obesity and diabetes have reached pandemic proportions and new therapeutic strategies are critically needed. Brown adipose tissue (BAT), a major source of heat production, possesses significant energy-dissipating capacity and therefore represents a promising target to use in combating these diseases. Recently, I discovered a novel link between circadian rhythm and thermogenic stress in the control of the conserved, calorie-burning functions of BAT. Circadian and thermogenic signaling to BAT incorporates blood-borne hormonal and nutrient cues with direct neuronal input. Yet how these responses coordinately shape BAT energy-expending potential through the regulation of cell surface receptors, metabolic enzymes, and transcriptional effectors is still not understood. My primary goal is to investigate this previously unappreciated network of crosstalk that allows mammals to effectively orchestrate daily rhythms in BAT metabolism, while maintaining their ability to adapt to abrupt changes in energy demand. My group will address this question using gain and loss-of-function in vitro and in vivo studies, newly-generated mouse models, customized physiological phenotyping, and cutting-edge advances in next generation RNA sequencing and mass spectrometry. Preliminary, small-scale validations of our methodologies have already yielded a number of novel candidates that may drive key facets of BAT metabolism. Additionally, we will extend our circadian and thermogenic studies into humans to evaluate the translational potential. Our results will advance the fundamental understanding of how daily oscillations in bioenergetic networks establish a framework for the anticipation of and adaptation to environmental challenges. Importantly, we expect that these mechanistic insights will reveal pharmacological targets through which we can unlock evolutionary constraints and harness the energy-expending potential of BAT for the prevention and treatment of obesity and diabetes. Fields of science medical and health scienceshealth sciencespublic healthepidemiologypandemicsmedical and health sciencesclinical medicineendocrinologydiabetesnatural scienceschemical sciencesanalytical chemistrymass spectrometrynatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsenzymesmedical and health scienceshealth sciencesnutritionobesity Programme(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Topic(s) ERC-StG-2014 - ERC Starting Grant Call for proposal ERC-2014-STG See other projects for this call Funding Scheme ERC-STG - Starting Grant Host institution KOBENHAVNS UNIVERSITET Net EU contribution € 1 497 007,51 Address NORREGADE 10 1165 Kobenhavn Denmark See on map Region Danmark Hovedstaden Byen København Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 1 497 007,51 Beneficiaries (1) Sort alphabetically Sort by Net EU contribution Expand all Collapse all KOBENHAVNS UNIVERSITET Denmark Net EU contribution € 1 497 007,51 Address NORREGADE 10 1165 Kobenhavn See on map Region Danmark Hovedstaden Byen København Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 1 497 007,51
